用于阻断冠状病毒感染和缓解炎症的抗原空间匹配聚aptamer 纳米结构

IF 19.1 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Chem Pub Date : 2024-11-21 DOI:10.1016/j.chempr.2024.10.021

Jingqi Chen, Yuqing Li, Xueliang Liu, Hongyi Li, Jiawei Zhu, Rui Ma, Linxin Tian, Lu Yu, Jiabei Li, Zhuang Liu, Weihong Tan, Yu Yang

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引用次数: 0

摘要

为应对未来可能出现的人类冠状病毒（HCoVs），需要开发多种有效的治疗策略。HCoVs 的症状和体征包括免疫炎症反应。因此，我们的研究重点是同时抑制 HCoV 感染和缓解肺部炎症。受构象表位匹配的启发，我们设计了一种全新的抗原空间匹配多肽aptamer（ASM-pApt）纳米结构，旨在与严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）伪病毒（PsV）上的多个尖峰（S）蛋白完美匹配。与单价aptamer相比，ASM-pApt纳米结构的解离常数（KD）降低了1000多倍，其病毒半抑制浓度（IC50）提高了10万多倍，达到89.7 fM（fmol/L），显示了抗原空间匹配的有效性。通过负载多酚作为抗炎药物和壳聚糖（CS）作为赋形剂，ASM-pApt 纳米结构显示出抗炎性和长效药物保留特性。我们的设计表明，聚aptamer有望在未来成为一种抗病毒/消炎候选药物，用于对抗新出现的HCoVs。

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Antigen spatial-matching polyaptamer nanostructure to block coronavirus infection and alleviate inflammation

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Antigen spatial-matching polyaptamer nanostructure to block coronavirus infection and alleviate inflammation

Preparation for the potential emergence of future human coronaviruses (HCoVs) calls for the development of versatile and effective treatment strategies. The signs and symptoms of HCoVs include an immune inflammatory response. Therefore, our study focuses on the simultaneous inhibition of HCoV infection and the alleviation of lung inflammation. Inspired by conformational epitope matching, we engineered a de novo antigen spatial-matching polyaptamer (ASM-pApt) nanostructure designed to align perfectly with multiple spike (S) proteins on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus (PsV). Compared with monovalent aptamer, the dissociation constant (K_D) of the ASM-pApt nanostructure decreased by over 1,000-fold, and its viral semi-inhibitory concentration (IC₅₀) improved by over 100,000-fold to 89.7 fM (fmol/L), indicating the effectiveness of antigen spatial matching. By loading polyphenol as anti-inflammatory drug and chitosan (CS) as an excipient, the ASM-pApt nanostructure showed anti-inflammatory and long drug retention properties. Our design shows the promise of polyaptamer as an antiviral/anti-inflammatory candidate against emerging HCoVs in the future.

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来源期刊

Chem Environmental Science-Environmental Chemistry

CiteScore

32.40

自引率

1.30%

发文量

281

期刊介绍： Chem, affiliated with Cell as its sister journal, serves as a platform for groundbreaking research and illustrates how fundamental inquiries in chemistry and its related fields can contribute to addressing future global challenges. It was established in 2016, and is currently edited by Robert Eagling.